Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib.
Adenocarcinoma; Aged; Alleles; Amino Acid Substitution; Antineoplastic Agents; Disease Progression; Drug Resistance, Neoplasm; Exons; Fatal Outcome; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Piperazines; Protein Kinase Inhibitors; Receptor, Epidermal Growth Factor; Tomography, X-Ray Computed; Treatment Outcome; Acquired resistance; EGFR; G724S; Lung cancer; Osimertinib; T790M
Mutations in the epidermal growth factor receptor (EGFR) are drivers for a subset of lung cancers. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) recently approved for the treatment of T790M-positive non-small cell lung cancer (NSCLC); however, acquired resistance to osimertinib is evident and resistance mechanisms remain incompletely defined. The EGFR G724S mutation was detected using hybrid-capture based comprehensive genomic profiling (CGP) and a hybrid-capture based circulating tumor DNA (ctDNA) assays in two cases of EGFR-driven lung adenocarcinoma in patients who had progressed on osimertinib treatment. This study demonstrates the importance of both tissue and blood based hybrid-capture based genomic profiling at disease progression to identifying novel resistance mechanisms in the clinic.
Oztan, A; Fischer, S; Schrock, A B; Erlich, R L; Lovly, C M; Stephens, P J; Ross, J S; Miller, V; Ali, S M; Ou, S-H I; and Raez, L E, "Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib." (2017). Journal Articles and Abstracts. 447.